Urinary Metal Exposure Linked to Increased Risk of Heart Failure, Landmark Study Finds

A new multi-cohort study by scientists at Columbia University Mailman School of Public Health has found that exposure to certain metals, detected in urine, is associated with a higher risk of heart failure (HF). Published in the Journal of the American College of Cardiology, it is the largest investigation of its kind to date, reinforcing the importance of reducing environmental metal exposure to reduce heart failure risk. While environmental metals are recognized as cardiovascular disease risk factors, until now, the role of metal exposure in heart failure risk has remained understudied.

“Most previous studies have assessed individual metals in isolation. By examining metals as a mixture, our analysis more closely reflects real-world exposure patterns,” said Irene Martinez-Morata, MD, PhD, postdoctoral research scientist in Environmental Health Sciences at Columbia Mailman School, and lead author. “In our analysis of over 10,000 adults across diverse geographic, racial, and ethnic backgrounds, we observed consistent associations between elevated urinary metal levels and increased HF risk over long-term follow-up after accounting for other established traditional risk factors for the disease, such as diabetes and obesity.”

The study pooled data from three large cohorts with more than 20 years of follow-up:

•  MESA (Multi-Ethnic Study of Atherosclerosis), U.S. adults aged 18–85 from six urban-suburban areas in Maryland, Illinois, North Carolina, California, Minnesota, and New York.
• SHS (Strong Heart Study), American Indian adults aged 18–65 in the U.S. from Oklahoma, Arizona, North Dakota, and South Dakota.
• Hortega Study, a general population cohort in Spain

Among the 10,861 participants—6,644 in MESA, 2,917 in SHS, and 1,300 in Hortega—a thousand people developed heart failure. In a subset, researchers assessed left ventricular function, which measures how effectively the heart pumps blood.

Metals were measured in urine samples, which can indicate how much metal is in the body and how much is being eliminated from it. Health and lifestyle data—including medication use, cholesterol levels, blood pressure, glucose, BMI, and more—were collected via questionnaires, lab tests, and physical exams. The team used advanced machine learning models to evaluate the combined effects of five urinary metals as a mixture.

Key findings included:

• Higher levels for the mixture of five metals in urine: arsenic, cadmium, molybdenum, selenium, and zinc, was associated with a 55 percent higher risk of heart failure in rural American Indian adults (SHS), a 38 percent higher risk in urban and suburban diverse populations (MESA) and a 8% increased risk in adults in Spain (Hortega).
• In the analysis of metals individually, a doubling in the levels of urine cadmium, a toxic metal found in tobacco products, foods and industrial waste, was associated with 15% higher risk of heart failure.
• Similarly, a doubling in the levels of molybdenum and zinc was associated with 13% and 22% higher risk of heart failure across the three cohorts. These metals have an essential function in the body, but high levels can be toxic.

“The strongest association between the 5-metal mixture and HF risk was seen in the SHS cohort,” said Martinez-Morata. “This population faces a historically high burden of contaminant metal exposure and cardiovascular disease, and public health action is urgently needed.”

The sources of exposure to these metals can vary from urban to rural environments. Toxic metals such as arsenic, cadmium, and tungsten can occur as a result of mining and industrial activity, leading to contamination of drinking water, foods that grow in contaminated soils, and air pollution. Many of these metals are also present in smoking devices, consumer products, and certain foods, observes Martinez-Morata and her co-authors. “Essential metals such as zinc and selenium are needed for biological functions, but high levels can be toxic,” they add. 

“We consistently found higher urinary levels of cadmium, molybdenum, and zinc linked to increased heart failure risk,” noted Ana Navas-Acien, MD, PhD, Columbia Mailman School professor and chair of the Department of Environmental Health Sciences. “Even after adjusting for diabetes—a known HF risk factor—the zinc association remained significant.”

These results support the relevance of metal exposures as contributors to heart failure risk. “In ongoing research, we aim to clarify biological mechanisms and to explore the role of environmental interventions in cardiovascular disease prevention,” said Navas-Acien, who is also the senior author.

“This study's strengths include its large, diverse sample size, high-quality data, and robust, long-term follow-up,” said Martinez-Morata. “Our findings underscore the importance of continuing efforts to monitor and reduce environmental metal exposures, particularly in communities with historically high exposure levels as an innovative approach to improve cardiovascular health.”

See the full list of co-authors, institutional affiliations, and funding sources in the published paper.